Lithium borohydride → (2R,3S,5S)-5-Hydroxymethyl-3-isopropyl-2-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1009832Notes

Reaction equation

HRID 1009832 reaction equation
CC[O:3][C:4]([C@@H:6]1[CH2:10][C@@H:9]([CH:11]([CH3:13])[CH3:12])[C@H:8]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[CH:15]=2)[N:7]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=O.[BH4-].[Li+]>O1CCCC1>[C:31]([O:30][C:28]([N:7]1[C@H:6]([CH2:4][OH:3])[CH2:10][C@@H:9]([CH:11]([CH3:13])[CH3:12])[C@@H:8]1[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH2:23][CH2:24][CH2:25][O:26][CH3:27])[CH:15]=1)=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 16124547(2S,4S,5R)-4-Isopropyl-5-[4-methoxy-3-(3-methoxy-propoxy)-phenyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester

Product 1

HCID 11998746(2R,3S,5S)-5-Hydroxymethyl-3-isopropyl-2-[4-methoxy-3-(3-methoxy-propoxy)phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 0.48 g of (2S,4S,5R)-4-Isopropyl-5-[4-methoxy-3-(3-methoxy-propoxy)-phenyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester VIIIa in 10 mL of tetrahydrofuran is cooled to 0° C. and a tetrahydrofuran solution of lithium borohydride (1.0 mL of a 2.0M solution) is added dropwise within 30 minutes. The mixture is stirred for a further 2 hours at 0° C. and quenched by addition of 0.2 mL of glacial acetic acid in 10 mL of tetrahydrofuran. The mixture is diluted with 20 mL of tert-butyl methyl ether and 20 mL of water and the organic phase separated. The organic phase is dried and the solvent removed to give the desired product as an oil. 1H-NMR δ (d6-DMSO/D2O, 300K) 6.90-6.80 (3H), 4.03-3.90 (3H), 3.80 (1H), 3.75 (3H), 3.55-3.45 (3H), 3.23 (3H), 3.05 (1H), 2.00-1.80 (3H), 1.65 (1H), 1.40 (9H), 1.20 (1H), 0.74 (6H).

Workup

  1. customquenched by addition of 0.2 mL of glacial acetic acid in 10 mL of tetrahydrofuran
  2. additionThe mixture is diluted with 20 mL of tert-butyl methyl ether and 20 mL of water
  3. customthe organic phase separated
  4. customThe organic phase is dried
  5. customthe solvent removed

Sources & evidence

ORD record
ord-0a887bfded19424d8c966c1ee6bb9232
Source dataset
uspto-grants-2011_07
Patent number
US07973175B2

Reaction notes

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